Previous computational evaluations of p\(K_A\)  have been based on either an implicit solvent model,
in which a solute molecule is embedded in a solvent described
by polarizable continuum medium,
[1]}, [2]}, [3]}, [4]}, [5]}, [6]}, [7]}, [8]}, [9]}, [10]}
or an explicit solvent model, in which both the solute
and the solvent are described explicitly as molecules.
[11]}, [12]}, [13]}, [14]}, [15]}, [16]}, [17]}, [18]}, [19]}
In general, the implicit solvent model is able to provide
p\(K_A\)  values with small computational effort but limited
accuracy.
The intrinsic error of the implicit solvent model arises from
the lack of complexity to describe solute-solvent interactions.
